Design and synthesis of potent and selective azaindole-based Rho kinase (ROCK) inhibitors.
ChemMedChem
; 3(12): 1893-904, 2008 Dec.
Article
en En
| MEDLINE
| ID: mdl-18973168
ABSTRACT
Rho kinase plays a pivotal role in several cellular processes such as vasoregulation, making it a suitable target for the treatment of hypertension and related disorders. We discovered a new compound class of Rho kinase (ROCK) inhibitors containing a 7-azaindole hinge-binding scaffold tethered to an aminopyrimidine core. Herein we describe the structure-activity relationships elucidated through biochemical and functional assays. The introduction of suitable substituents at the 3-position of the bicyclic moiety led to an increase in activity, which was required to design compounds with favorable pharmacokinetic profile. Azaindole 32 was identified as a highly selective and orally available ROCK inhibitor able to cause a sustained blood pressure reduction in vivo.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores Enzimáticos
/
Quinasas Asociadas a rho
/
Indoles
Límite:
Animals
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania